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Biomedical subjects

D Pratt

Publications and source records attributed to D Pratt.

At least 37 records · Page 2Linked to original sources

Gynaecoradiological uterine resection.

We assessed the feasibility of performing uterine surgery under fluoroscopic control in an ambulatory setting that does not require operating room time and general anaesthesia. Four uterine septae were resected and two cases of Asherman's syndrome were treated using fluoroscopically guided scissors. All six surgical procedures were successfully completed. Gynaecoradiological uterine resection (GUR) procedures, utilizing fluoroscopy guided scissors, are promising new techniques, which may allow the successful performance of uterine surgery in a cost effective ambulatory setting with no requirement of general anaesthesia.

Ambulatory Care↗

[What do we really know about autoantibody abnormalities and reproductive infertility? A critical review].

UNLABELLED: The diagnosis and treatment of autoantibody-associated forms of reproductive failure is critically reviewed. OBJECTIVE: To critically evaluate the published literature in reference to autoantibody-associated forms of reproductive failure. LOCATION: Medical School-affiliated private Infertility Center. MATERIALS: A review of over 200 published reflecting on the topic. RESULTS: Autoantibody associated reproductive failure, characterized by a decrease in fecundity and an increase in the risk of pregnancy loss, appears established. Autoantibody abnormalities, as routinely detected by standard laboratory assays, are, however, neither immunologically nor biologically specific since cross reactivities between autoantibodies are frequent and a specific autoantibody may cause a biological effect in one but not in another affected individual. CONCLUSIONS: The evaluation of autoantibody abnormalities in all cases of suspected autoimmune-associated reproductive failure is valuable and will improve clinical care of affected patients. Clinicians need, however, to recognize the limitations of autoantibody testing and have to adjust their clinical management to the degree and quality of autoantibody evaluation available to them in their community.

Antibodies, Antiphospholipid↗

Effects of gamma-irradiation on the M-CSF-promoter linked to a chloramphenicol aminoacyl transferase reporter gene expressed in a clonal murine bone marrow stromal cell line.

The effects of cytokines produced by bone marrow stromal cells on closely associated hematopoietic cells constitute a major component of the physiology of the hematopoietic microenvironment. A major cytokine produced by marrow stromal cells is macrophage colony-stimulating factor (M-CSF). To determine the effect of gamma-irradiation on the M-CSF promoter in bone marrow stromal cells, we selected a clonal cell line from the C3H/HeJ mouse marrow stromal cell line D2XRII and stably transfected a reporter construct containing the murine M-CSF-promoter linked to a chloramphenicol aminoacyl transferase (CAT) gene. CAT activity was measured at serial time points after gamma-irradiation in vitro to doses between 500 and 10,000 cGy at a dose rate of 116 cGy/min. D2XRII marrow stromal cells treated with phorbol myristate acetate (40 micrograms/ml, four h), demonstrated a significant two-fold increase in CAT activity. In contrast, CAT activity measured immediately, 24 h, 72 h or 1 week after gamma-irradiation, showed no significant increase or decrease in CAT activity. An increase in CAT activity was detected 48 h after irradiation with cells that received 5,000 cGy. Thus, single fraction gamma-irradiation of plateau phase bone marrow stromal cells did not decrease M-CSF-promoter activity. These results are consistent with prior experimental data demonstrating stable levels of release of M-CSF protein following gamma-irradiation of bone marrow stromal cells and imply that the stability of transcription of the gene for this important cytokine is protected from irradiation.

Animals↗

Autoantibody profiles and immunoglobulin levels as predictors of in vitro fertilization success.

OBJECTIVE: Our aim was to determine the predictive value of autoantibody and immunoglobulin determinations as indicators of the success of in vitro fertilization. STUDY DESIGN: This was a blinded study in which laboratory evaluations were performed on coded samples obtained from another institution. Codes were broken and data were analyzed after results of all laboratory tests had been reported out. One hundred five infertility patients who had undergone in vitro fertilization were randomly chosen. Among those, 46 were considered low responders (six or fewer oocytes were retrieved) and 59 as high responders (13 to 30 oocytes were retrieved). Total immunoglobulin G, M, and A levels and 15 autoantibody levels (6 antiphospholipids, 5 antihistones, and 4 antipolynucleotides) were determined separately for immunoglobulin G, immunoglobulin M, and immunoglobulin A isotypes. RESULTS: High and low responders demonstrated an unusual incidence of autoantibody (25% and 30%, respectively) and immunoglobulin (46% and 48%, respectively) abnormalities. They did not differ from each other, however, in either immunoglobulin or autoantibody parameters. Autoantibody and immunoglobulin abnormalities alone or in combination did not predict pregnancy success (24% vs 16%), incidence of chemical pregnancies (15% vs 24%), or clinical pregnancy loss (9% vs 11%) when such women were compared with those without either abnormality. However, the occurrence of hypergammaglobulinemias, in contrast to hypogammaglobulinemias, was associated with a significant decrease in the clinical pregnancy rate (6% vs 24%, p = 0.05). CONCLUSIONS: Neither autoantibody abnormalities nor total immunoglobulin abnormalities allow differentiation between high and low responders in in vitro fertilization cycles. The presence of autoantibody and total immunoglobulin abnormalities also does not predict low clinical pregnancy rates. Within a group of women with immunoglobulin abnormalities, those with hypergammaglobulinemias appear, however, at significant risk for low pregnancy rates with in vitro fertilization. This observation suggests that high total immunoglobulin levels may serve as a marker for an as yet to be determined immunologic factor that adversely affects the chance of conception. The evaluation of total immunoglobulin levels may be indicated as part of a routine infertility workup.

Adult↗

Laparoscopic removal of twin cornual pregnancy after in vitro fertilization.

The laparoscopic management of tubal pregnancies by salpingostomy has become a clinical standard of care (5). Those surgeries usually are performed for tubal pregnancies that are located distally to the cornua and the intramural piece of the tube. We previously reported on the conservative surgical management of interstitial pregnancies (3). To our knowledge, cornual pregnancies have never before been approached laparoscopically. Such a surgical approach is reported here, involving a twin gestation in the left uterine cornua conceived by IVF in a women with bilaterally absent tubes.

Adult↗

Wire guide cannulation alone is no treatment of proximal tubal occlusion.

Tubal catheterization procedures have become standard of care as a primary treatment of proximal tubal occlusions. They successfully utilize a variety of catheter techniques, though all usually include a wire guide. This raises the question whether guide wire catheterizations alone can be used to treat proximal tubal occlusions. We therefore investigated consecutively 25 women with at least one proximally occluded oviduct by attempting wire guide cannulations bilaterally in 10 and unilaterally in 12 women with two tubes and in three women with a single tube. Among the 10 patients with bilateral occlusion, seven were recanalized bilaterally (70%), one unilaterally (10%) and two not at all (20%). Among the 15 patients with unilateral tubal occlusion, 12 (80%) were recanalized. In total, 27 out of 35 (77%) obstructed oviducts were recanalized. In a follow-up period of 5-17 months only one pregnancy was, however, recorded and this was a tubal pregnancy. We conclude that wire guide cannulation of proximally obstructed tubes achieves tubal patency in a large percentage of cases, comparable to other catheter techniques reported in the literature. In contrast to those, however, wire guide cannulations alone result in much lower pregnancy rates. This observation strongly suggests that wire guides, used with co-axial and balloon catheter systems, are not responsible for the pregnancy success reported for these procedures. Wire guide cannulation alone does not therefore represent adequate treatment for patients with proximally occluded Fallopian tubes.

Catheterization↗

Antithyroid antibodies and the association with non-organ-specific antibodies in recurrent pregnancy loss.

OBJECTIVES: The purpose of our study was to evaluate the incidence of antithyroid antibodies and non-organ-specific antibodies in women who have had three or more recurrent spontaneous abortions. STUDY DESIGN: Sera from 45 women for the presence of antithyroid antibodies to thyroglobulin and thyroid peroxide and for the non-organ-specific autoantibodies to 6 phospholipids, 5 histones, and 4 polynucleotides were analyzed. Sera from 100 apparently health blood donors served as controls. RESULTS: The test results of 14 (31%) of 45 study subjects were positive for one or both antithyroid antibodies compared with 19 (19%) of controls. Five (11%) of 45 patients had positive test results for one or more non-organ-specific antibodies, and 4 (8%) of 45 had positive test results for the lupus anticoagulant by either activated partial thromboplastin, tissue thromboplastin time, or both. Only 3 (21%) of 14 subjects whose test results were positive for thyroid antibodies also demonstrated non-organ-specific autoantibodies. COMMENTS: The incidence of antithyroid antibodies in women who have had recurrent abortions appears not to be significantly increased compared with a normal random control population. Antithyroid antibodies do occur, however, with significantly greater frequencies in women with recurrent spontaneous abortions than non-organ-specific autoantibodies (p = 0.02). Organ-specific and non-organ-specific autoantibodies may serve as independent markers of risk for repeated pregnancy loss in patient populations where pregnancy loss is associated with abnormal autoimmune function.

Abortion, Habitual↗

Virologic markers of human immunodeficiency virus type 1 in cerebrospinal fluid. The HIV Neurobehavioral Research Center Group.

As part of a longitudinal study, 265 cerebrospinal fluid (CSF) specimens from 204 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects and 43 seronegative controls were evaluated. Of the 204 seropositive persons, 78 (38%) had > or = 1 CSF culture positive for HIV-1; the probability of being culture positive increased as the number of CSF samples obtained increased (P = .0018). Significantly correlated with culture positivity were elevations in CSF protein level (P = .014) and CSF white blood cell count (P = .001). Virus was more readily cultured from clarified CSF (89%, 42/47) than from the cellular fraction (30%, 14/47; P < .00001). Amplification of HIV-1 DNA by polymerase chain reaction (PCR) from 25 seropositive persons was positive in 9 (82%) of 11 culture-positive and in 4 (29%) of 14 culture-negative specimens, while amplification of viral RNA detected all 11 culture-positive and 9 (64%) of the 14 culture-negative CSF specimens. These data support the hypothesis that the development of HIV-1-associated neurocognitive disorders are not dependent solely on the presence of HIV-1 within the central nervous system.

Adult↗

What do we really know about autoantibody abnormalities and reproductive failure: a critical review.

CONDENSATION: The diagnosis and treatment of autoantibody-associated forms of reproductive failure is critically reviewed. OBJECTIVE: To critically evaluate the published literature in reference to autoantibody-associated forms of reproductive failure. LOCATION: Medical School-affiliated private Infertility Center. MATERIALS: A review of over 200 published papers reflecting on the topic. RESULTS: Autoantibody associated reproductive failure, characterized by a decrease in fecundity and an increase in the risk of pregnancy loss, appears established. Autoantibody abnormalities, as routinely detected by standard laboratory assays, are, however, neither immunologically nor biologically specific since cross reactivities between autoantibodies are frequent and a specific autoantibody may cause a biological effect in one but not in another affected individual. CONCLUSIONS: The evaluation of autoantibody abnormalities in all cases of suspected autoimmune-associated reproductive failure is valuable and will improve clinical care of affected patients. Clinicians need, however, to recognize the limitations of autoantibody testing and have to adjust their clinical management to the degree and quality of autoantibody evaluation available to them in their community.

Abortion, Habitual↗

Abnormal (auto)immunity and endometriosis.

Immunologic abnormalities may precede endometriosis and be involved in its pathophysiology especially as it relates to the occurrence of infertility and pregnancy loss. Many cases of unexplained infertility may represent undiagnosed endometriosis. This is supported by the observation that immunologic profiles in endometriosis and unexplained infertility are very similar. It is argued that endometriosis is a systemic rather than local disease, thus requiring systemic therapy. Currently available medical and surgical techniques are effective in relieving symptomatology associated with endometriosis, although this is often temporary. A new clinical approach is needed that considers systemic presentation and likely immunologic pathophysiology.

Abortion, Spontaneous↗

Cloning and sequence comparisons of four distinct cysteine proteases expressed by Haemonchus contortus adult worms.

Three new members of a developmentally regulated cysteine protease gene family of the parasitic nematode Haemonchus contortus have been isolated and characterized. One of the new genes, AC-3, was found to be linked in tandem to the previously characterized AC-2 gene. Nucleotide sequence analyses revealed that the first 90 amino acids of AC-3 are organized into four exons, similar to the situation in AC-2. A cDNA that appears to be a near full-length copy of the AC-3 gene was isolated using the polymerase chain reaction (PCR) technique to amplify cDNAs from adult worm poly(A)+ mRNAs. In addition to AC-3, a distinct cysteine protease cDNA, AC-4, was amplified by the same oligonucleotide primers. cDNAs encoding a fifth cysteine protease, AC-5, were isolated from an adult worm cDNA expression library using specific rabbit antisera and by PCR. Comparison of the predicted amino acid sequences of AC-3, AC-4 and AC-5 reveal that they share 64-77% identity with one another and with the previously reported AC-1 and AC-2 sequences. The amino acids surrounding the active site cysteine are highly conserved, as are the positions of other cysteine residues in the mature protein sequences. The H. contortus proteases are more similar to one another than they are to human cathepsin B (38-44% amino acid identity) or to the Sm31 cysteine protease of Schistosoma mansoni (36-40% identity). Our studies indicate that H. contortus adult worms express mRNAs for several distinct cysteine proteases. The significant primary sequence differences between the proteases suggest that they differ in their substrate specificities and precise physiological functions.

Amino Acid Sequence↗

Isolation of putative cysteine protease genes of Ostertagia ostertagi.

Recombinant phage containing putative Ostertagia ostertagi cysteine protease genes have been isolated from a lambda EMBL-3:genomic DNA library using a Haemonchus contortus cathepsin B-like cysteine protease cDNA as hybridization probe. Restriction enzyme maps of the phages suggest that they identify at least 3 genes, 2 of which appear to be linked in tandem. The complete nucleotide sequence of one gene, CP-1, was determined. The CP-1 gene appears to be organized into 12 exons than span 4.5 kb of DNA. The number and sizes of the exons are essentially identical to those in the H. contortus AC-2 cysteine protease gene. Partial nucleotide sequences obtained for a second O. ostertagi gene, CP-3, revealed a similar organization for exons 8-12 in this gene. Like other cathepsin B-like cysteine proteases, CP-1 appears to be synthesized initially as a preproprotein that is proteolytically processed to its mature form. The amino acid identity between the presumptive CP-1 and CP-3 proteins is 66%, which is similar to the level of homology between the presumed mature protein regions of CP-1 and AC-2. Amino acid identity between CP-1 and AC-2 is greatest in the mature protein region and lowest in the signal sequence and propeptide regions. The CP-3 protein appears to be most closely related to the H. contortus AC-5 protein. CP-1 and CP-3 display significantly greater homology to H. contortus cysteine proteases than they do to human cathepsin B or the Sm31 cysteine protease of Schistosoma mansoni (about 40% identity with each).

Amino Acid Sequence↗